Kidney disease can be progressive, leading to end-stage renal disease and, ultimately, death. End-stage renal disease affects approximately 650,000 human patients each year worldwide and treatment costs have been estimated to be about twenty billion dollars (Klahr, S., Contrib. Nephrol. 118:1-5 (1996)).
Current methods to diagnose kidney disease and, in particular, progressive kidney disease, include monitoring urine for elevated protein levels and conducting renal biopsies. Available treatments for kidney disease, specifically progressive kidney disease, include the use of steroids, alkylating agents and cyclosporine (de Mattos, A. M. et al., pages 861-885, In: “Immunologic Renal Diseases,” eds. Neilson, E. G. et al., Lippincott-Raven Publishers, Philadelphia, Pa. (1997)). The above mentioned diagnostic methods often are inadequate since significant damage to the kidney can occur prior to diagnosis. Likewise, the above mentioned treatments frequently are unsuccessful in halting the progression of kidney disease and, therefore, unsatisfactory, since they often are accompanied by adverse side effects, such as cellular and systemic toxicity.
Although animal models have been used to study some kidney diseases, animal models suffer from a number of limitations when extended to human kidney disease diagnosis and treatment. For example, animal models of kidney disease do not necessarily depict kidney disease in humans and the administration of steroids, although reasonably effective in the treatment of kidney disease in experimental animal models, are relatively ineffective in the treatment of kidney disease in humans (Siegel, N. J. et al., Kidney Int. 25:906-911 (1984); Cronin, R. E., et al., Am. J. Physiol. 248:F332-F339 (1985); Cronin, R. E., et al., Am. J. Physiol. 251:F408-F416 (1986); Seiken, G. et al., Kidney Int. 45:1622-1627 (1994); Shaw, S. G. et al., J. Clin. Invest. 80:1232-1237 (1987); Allgren, R. L. et al., N. Eng. J. Med. 336:828-834 (1997); Paller, M. S., Sem. Nephrol. 18:482-489 (1998); Savill, J., et al., In: “Oxford Textbook of Clinical Nephrology”, eds. Davison, A. M., et al., Oxford Medical Publications, page 403-439 (1998); Hirschberg, R. et al., Kidney Int. 55:2423-2432 (1999)). Thus, animal model systems generally can not be used to define and identify methods which halt the progression, reduce the severity, treat, or diagnose progressive kidney disease in humans. Thus, there is a need to develop new, improved and effective methods of reducing the severity, diagnosing and treating kidney disease in humans.